Fig. 4. Light micrograph of rat sciatic nerve injected with 600 mm/approximately 15% lidocaine alone ( A ) or coadministered with p38 mitogen-activated protein kinase inhibitor SB203580 ( B ). Magnification: bar represents 20 μm. ( A ) Lidocaine, 15%, applied to the rat sciatic nerve caused severe wallerian degeneration as seen in tissue studied by light microscopy 7 days after drug administration. Hydropic and swollen axons were prevalent throughout the tissue, and degenerated nerve fibers were seen throughout all fascicles of the nerve. There was myelin blebbing and macrophage phagocytosis of the degenerated tissue. Epineurial and endoneurial collagen was also significantly increased, and the vasculature appeared occluded. ( B ) In contrast, animals receiving 15% lidocaine with SB203580 displayed much less tissue damage, which consisted primarily of edema that separated otherwise normal nerve fibers. There was activation of some fibroblasts and Schwann cells and a degree of demyelination; however, the majority of the axons in the tissue studied seemed to be protected from wallerian degeneration by the addition of SB203580.